Our work further uncovered a novel component of the epigenetic regulatory network that underlies the balanced state of rDNA clusters. In spite of previous reports on the potential role of Mybbp1a in gene regulation, demonstration of its func tional Enzalutamide prostate cancer significance in cells has been largely elusive. A re cent study showed that Mybbp1a is downstream of the Aurora B kinase signaling and plays an essential role in the normal progression of mitosis. Furthermore, Mybbp1a was recently found to signal a response to nu cleolar stress by facilitating the p300 dependent acetyl ation and activation of p53. In addition, Mybbp1a has been linked, via PGC 1 and Prep1, to mitochon drial respiration and insulin mediated glucose uptake in muscle, thus strengthening a relevant role of Mybbp1a in cellular metabolism.

Collectively, these studies insinuate that Mybbp1a is an important cellular factor with pleiotropic functions. Our present study pro vides further support to this possibility by establishing a previously unrecognized link of the Mybbp1a protein to ribosomal RNA expression regulation. Its nucleolar function may thus underpin proper protein production and cell proliferation. Due to tight coordination between ribosome biogen esis and cell proliferation and metabolism, transcription of rRNA and stable maintenance of rDNA clusters are thought to be under intricate control by intercalated mechanisms, particularly at the epigenetic level. Various chromatin remodeling and modifying activities with a role in rDNA transcription have been identified. To such regulatory networks, we have added a new important one.

The observed functional attributes of Mybbp1a are in accordance with those previously reported for other rDNA associated epigenetic repres sors, such as JHDM1B and energy dependent nucle olar silencing complex. Interestingly, an energy sensing nucleolar pathway involving eNoSC and Mybbp1a was recently implicated in the nucleolar stress associated regulation of p53. Possible func tional and physical interaction between Mybbp1a and these factors may thus contribute to a robust and dy namic expression of the ribosomal RNA. However, while GSK-3 an upregulation of rRNA may be accompanied by greater extent of cellular proliferation and sometimes an increase in cell size, as shown in the case of JHDM1B, knockdown of Mybbp1a led to instead a slower cell growth and slighted delayed G1 S phase progression. This discrepancy may be explained by the potentially multifunctional nature of Mybbp1a, abro gation of which may elicit compensatory changes that culminate in cell growth arrest and/or defect. In addition, disturbance of nucleolar content as a conse quence of rRNA accumulation may also activate stress signal cascades that ultimately restrain cell growth.